1. Field of the Invention
The invention relates to a process for the preparation of 2-substituted 5-nitroso-2,6-diaminopyrimidines.
2. Prior Art
It is known that 5-nitroso-2,4,6-triaminopyrimidine can be prepared from malonic dinitrile and a guanidine salt.
2,4,6-Triaminopyrimidine is obtained in moderate yield by the condensation of malonic dinitrile and guanidine hydrochloride or nitrate in the presence of a sodium alcoholate in alcoholic solution [W. Traube, Ber. 37, 4544 (1904); H. Sato et al., J. Chem. Soc. Japan Pure Chem. Sect. 72, 866 (1951); and Chem. Abstr. 47, 5946 (1953)]. This pyrimidine is then nitrosated to 5-nitroso-2,4,6-triaminopyrimidine, using nitrous acid [M. F. Mallette et al., J. Am. Chem. Soc. 69, 1814 (1947)]. such processes have the disadvantages that they are too troublesome when relatively large amounts have to be prepared and that the maximum yield of 5-nitroso-2,4,6-triaminopyrimidine is 75 to 78 percent, relative to malonic dinitrile.
Attempts have been made to simplify the process by not isolating the intermediate product 2,4,6-triaminopyrimidine (see Swiss Patent Specification No. 630,616 or U.S. Pat. No. 4,145,548). However, the process still has various disadvantages: expensive sodium alchololate has to be used; at least two mols of salt (NaCl and Na acetate) are precipitated per mol of malonic dinitrile employed; the reaction has to be carried out using relatively dilute solutions (approximately 2 liters of solvent per mol of product); and finally, the recovery of the solvent is a very difficult procedure, since a 4-component solvent mixture (methanol, ethanol, glacial acetic acid, water and by-products) is present.
Another route for the preparation of 5-nitroso-2,4,6-triaminopyrimidine is described by E. C. Taylor, O. Vogl and C. C. Cheng in J. Am. Chem. Soc. 81, 2442 (1959). 5-Nitroso-2,4,6-triaminopyrimidine is obtained in 88 percent yield by heating the potassium salt of isonitroso-malononitrile with guanidine carbonate in dimethylformamide. Since the potassium salt is prepared from the silver salt of isonitrosomalononitrile, the process is unsuitable for large-scale industrial production.
French Patent Specificaion No. 1,364,734 describes a process in which first malonic dinitrile in aqueous acetic acid solution is nitrosated with sodium nitrite, and then the resultant isonitrosomalononitrile solution is treated with guanidine carbonate, CO.sub.2 being evolved and the guanidine salt of isonitrosomalononitrile being obtained by precipitation. The salt suspension is then cooled to approximately 0.degree. C. and filtered, and the guanidine salt of isonitrosomalononitrile is dried. After the addition of K.sub.2 CO.sub.3 to the salt in dimethylformamide, the mixture is heated under reflux in order to effect isomerization to 5-nitroso-2,4,6-triaminopyrimidine.
Such process represents a certain degree of progress compared with the process according to Taylor et al., but it still has several disadvantages. Thus, the acetic acid has to be used in excess (10 percent, according to the example). This excess has to be neutralized with guanidine carbonate in order for the formation of the guandine salt of isonitrosomalononitrile to go to completion.
Cooling the aqueous suspension to approximately 0.degree. C. involves technical difficulties, since a crust of ice is formed on the inside of the reaction vessel. When the mixture is cooled to temperatures which are not quite so low, the salt is not completely precipitated.
From the point of view of safety, drying the guanidine salt of isonitrosomalononitrile involves risks.
In the treatment of crude isonitrosomalononitrile solution with guandine carbonate, one equivalent of CO.sub.2 is liberated. The reaction mixture therefore has a tendency to foam during the operation and accordingly the reaction vessel cannot be optimally utilized.